| Home > Publications database > Six-month evaluation of normal mouse brain side effects: Comparing FLASH and conventional proton partial brain irradiation |
| Journal Article | DKFZ-2026-01181 |
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2026
Elsevier
Amsterdam
Abstract: Background and purpose: Preclinical studies demonstrated ultra-high dose-rate radiation treatment ability toeffectively control local tumour growth while reducing damage to healthy tissues. This methodological pilotstudy was designed and conducted to establish an irradiation setup and to generate data for future studiesinvestigating long-term side effects of mouse brain irradiation with proton FLASH (FLASH-PT) and conventionalproton therapy (CONV-PT).Material and methods: Fourteen C57BL/6JRj female mice were partial brain irradiated with a single dose of 22.5Gy using a proton spread-out Bragg peak (SOBP). Mice were randomised into FLASH-PT (268 Gy/s, n = 6),CONV-PT (0.27 Gy/s, n = 6), and unirradiated sham groups (n = 2). In addition to skin reaction monitoring asshort-term endpoint, regular contrast-enhanced magnetic resonance imaging (MRI) was performed during thesix-month follow-up. Brains were formalin-fixed and paraffin-embedded and stained to assess activation ofmicroglia.Results: The analysis of skin reactions demonstrates a trend in tissue-sparing effect for the FLASH group. In thebrain MRI, no contrast enhancement was observed after irradiation. Although no group–level differences inmicroglia activation were observed between FLASH-PT and CONV-PT, both treatments showed increased densityof activated microglia, which was distinct in specific regions within the periventricular area.Conclusion: The established irradiation setup allowed for a clinically relevant approach to preclinical FLASH-PTresearch. Partially irradiated brain showed no microglia-related FLASH effect. Further studies are required tofully comprehend dose–effect curves and timing for the FLASH effect in the brain.
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